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Specialized Pro-Resolving Lipid Mediators: Emerging Therapeutic Candidates for Multiple Sclerosis.
Clinical Reviews in Allergy & Immunology ( IF 9.1 ) Pub Date : 2020-06-03 , DOI: 10.1007/s12016-020-08796-4
Insha Zahoor 1 , Shailendra Giri 2
Affiliation  

Multiple sclerosis (MS) is a neuroinflammatory disease in which unresolved and uncontrolled inflammation disrupts normal cellular homeostasis and leads to a pathological disease state. It has long been recognized that endogenously derived metabolic by-products of omega fatty acids, known as specialized pro-resolving lipid mediators (SPMs), are instrumental in resolving the pathologic inflammation. However, there is minimal data available on the functional status of SPMs in MS, despite the fact that MS presents a classical model of chronic inflammation. Studies to date indicate that dysfunction of the SPM biosynthetic pathway is responsible for their altered levels in patient-derived biofluids, which contributes to heightened inflammation and disease severity. Collectively, current findings suggest the contentious role of SPMs in MS due to variable outcomes in biological matrices across studies conducted so far, which could, in part, also be attributed to differences in population characteristics. It seems that SPMs have neuroprotective action on MS by exerting proresolving effects on brain microglia in its preclinical model; however, there are no reports demonstrating the direct effect of SPMs on oligodendrocytes or neurons. This reveals that “one size does not fit all” notion holds significance for MS in terms of the status of SPMs in other inflammatory conditions. The lack of clarity served as the impetus for this review, which is the first of its kind to summarize the relevant data regarding the role of SPMs in MS and the potential to target them for biomarker development and future alternative therapies for this disease. Understanding the mechanisms behind biological actions of SPMs as resolution mediators may prevent or even cure MS and other neurodegenerative pathologies.



中文翻译:

专业的促分解脂质介质:多发性硬化症的新兴治疗候选药物。

多发性硬化症 (MS) 是一种神经炎症性疾病,其中未解决和不受控制的炎症会破坏正常的细胞稳态并导致病理疾病状态。长期以来人们已经认识到,欧米茄脂肪酸的内源性代谢副产物,称为专门的促分解脂质介质 (SPM),有助于解决病理性炎症。然而,尽管 MS 是慢性炎症的经典模型,但关于 MS 中 SPM 功能状态的可用数据很少。迄今为止的研究表明,SPM 生物合成途径的功能障碍是其在患者来源的生物体液中水平改变的原因,这会导致炎症和疾病严重程度的加剧。总的来说,目前的研究结果表明,由于迄今为止进行的研究中生物基质的可变结果,SPMs 在 MS 中的作用存在争议,这在一定程度上也可归因于人群特征的差异。SPM 似乎通过在其临床前模型中对脑小胶质细胞发挥促消退作用而对 MS 具有神经保护作用;然而,没有报告证明 SPM 对少突胶质细胞或神经元的直接影响。这表明,就 SPM 在其他炎症条件下的状态而言,“一刀切”的概念对 MS 具有重要意义。缺乏明确性是这次审查的动力,这是第一个总结有关 SPM 在 MS 中的作用的相关数据以及将它们作为生物标志物开发和未来替代疗法的潜力。了解 SPM 作为分解介质的生物学作用背后的机制可以预防甚至治愈 MS 和其他神经退行性疾病。

更新日期:2020-06-03
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